The long-term objective of the study is the development of new approaches to pneumococcal vaccination that will provide better protection to patients with impaired immunity. Streptococcus pneumoniae is a pathogen responsible for great morbidity and mortality in different populations. The increase of antibiotic resistance to this and other bacteria, and the fact that current pneumococcal vaccines are not completely effective accentuate the need for better vaccines. Increased susceptibility to pneumococcal infection is particularly evident in immune impaired groups such as HIV+ individuals, newborns, bone marrow recipients, and the elderly, though S. pneumoniae causes disease in both immunocompetent and immunocompromised individuals. This proposal will use the phage-displayed technology to identify peptide mimotopes that bind to antibodies reactive with the capsular polysaccharide of serotype 8 pneumococcus (PPS-8). The peptides will be used as vaccine targets to determine if they elicit protective antibody responses in experimental pneumococcal infection. SCID-hu mice will be utilized to study the antibody responses to the peptides. Thus, human antibody responses can be studied. In addition, the reagents generated can be used to study the specificity of vaccine elicited antibodies in different patient groups.